The objective of this proposal is to investigate the possible role of coregulators in gene expression regulated by progesterone receptor and thyroid hormone receptor. Steroid hormones and thyroid hormones are important for growth, cell differentiation, and development in vertebrates. Hormone responses are initiated by the binding of hormone to its nuclear receptor. Subsequently, nuclear receptors (TR, PR) function as transcription factors to regulate the expressions of specific genes by direct or indirect (via coregulators) interactions with the transcriptional machinery at promoters. It has been shown that coregulators are involved in multiple signaling pathway, and participate in nuclear receptor actions within the cell. The aims of this proposal are to isolate coregulator-associated proteins, to characterize these associated proteins, as well as to study the in-vivo functions of coregulators and their associated proteins. This study will address the following questions: What are the other cellular proteins that associate with coregulators? What is the possible role of these associated factors in the function of coregulators? This study will help us better understand the functions of coregulators and eventually, the mechanism of steroid hormone action.